1. Field of the Invention
The present invention provides the novel crystalline bisulfate salt of the azapeptide HIV protease inhibitor of the formula ##STR2## which exhibits unexpectedly superior aqueous solubility/dissolution behavior compared to other salts, and significantly improved oral bioavailability in animals compared to the free base. The bisulfate salt is thus useful for pharmaceutical dosage forms of the above-indicated protease inhibitor, particularly oral dosage forms.
2. Background Art
Published PCT patent application WO 97/40029 discloses a series of azapeptide HIV protease inhibitors reported to have a high degree of inhibitory activity against the HIV virus. One of the agents included within the scope of WO 97/40029 is the compound having the structural formula ##STR3## and the chemical name [3S-(3R*, 8'R*, 9'R*, 12R*)]-3,12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6 -[[4-(2-pyridinyl)phenylmethyl]-2,5,6,10,13-pentaazatetradecanedioic] acid, dimethyl ester and is under evaluation as a possible second generation HIV protease inhibitor.
WO 97/40029 discloses the free base form of azapeptide derivatives such as compound I and also various pharmaceutically acceptable acid addition salts. While several organic and inorganic acids are mentioned as possible salt-forming agents, including sulfuric acid, there is no mention of the particular bisulfate salt which is the subject of the present application.